We propose to identify and analyze the underlying mechanistic pathway of X-linked microphthalmia/anophthalmia. This is a heterogeneous group that includes syndromic microphthalmia 1 (MCOPS1) OMIM #309800, and syndromic microphthalmia 2 (MCOPS2) OMIM #300166 and other, as yet to be defined, malformations of the globe. We have identified a causative gene for MCOPS1 (Ng, et al 2004). To further delineate these conditions, we will study families with these features through a combined clinical and molecular approach. Specimens will be collected and evaluated in the laboratory by linkage analysis, physical mapping, candidate gene characterization, mutation screening, genotype-phenotype correlation, and cell biologic studies of normal and mutant proteins.